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RCOG release: More research is needed into the role of natural killer cells in fertility and the benefits of endometrial scratch

News 28 November 2016

Two new scientific opinion papers published today by the Royal College of Obstetricians and Gynaecologists (RCOG) call for more high quality research into the role of natural killer cells in fertility and the effect of endometrial scratching on pregnancy outcomes.

Scientific Impact Papers (SIP), are up-to-date reviews of emerging or controversial scientific issues. The first paper looks at the role of uterine natural killer (uNK) cells, how they are measured, the role of testing and the evidence behind any links to improving implantation rates and early placental development.

The paper clarifies that uNK cells are different from peripheral blood (PB) natural killer (NK) cells, and that measurements of the latter are of limited value in aiding our understanding of the role of uNK cells in reproductive failure.

The paper states that despite much research, the role of uNK cells in pregnancy remains uncertain. The authors add that there is no indication to offer routine uNK cell testing in women presenting with infertility or seeking IVF treatment, more evidence is needed in this area and testing in women with recurrent miscarriage and recurrent implantation failure should be regarded as experimental.

Testing also has a number of limitations as currently there is a lack of consensus on the methods used for measuring and reporting uNK cell numbers, lack of a clear definition of a ‘normal’ range and uncertainty around the significance of higher levels of uNK cells linking to adverse pregnancy outcome.

Possible treatments offered to women with abnormal uNK cell numbers includes intravenous immunoglobulin (IVIg) administered during pregnancy, states the paper. However, the evidence suggests that treatment with IVIg is not supported by the current evidence and, since it may have serious adverse effects, should not be used.

Other treatments offered include the use of glucocorticoids. One small observational study involving 29 women showed that administration of prednisolone, a type of corticosteroid, led to a reduction in uNK cell numbers. The evidence for treatment with glucocorticoids however remains inconclusive at present, state the authors.

The second opinion paper explores the effect of endometrial scratch on pregnancy outcomes in women who have experienced recurrent miscarriage and recurrent implantation failure.

Endometrial scratch is a procedure which is hypothesised to help embryos implant more successfully after IVF, and intracytoplasmic sperm injection (ICSI) and involves injuring (scratching) the lining of the womb.

Several studies have examined the impact of endometrial scratch in the cycle preceding an IVF treatment cycle in women with recurrent implantation failure, which appear to provide convincing evidence of benefit of superficial endometrial scratch in improving the implantation rate in this group of women. However, the effect of this treatment on pregnancy outcomes in women who have experienced recurrent miscarriage has not yet been evaluated.

Moreover, the authors state that current evidence on the value of the procedure in women undergoing their first IVF cycle is lacking.

Professor Adam Balen, Chair of the British Fertility Society (BFS) and spokesperson for the RCOG, said:

“These two papers look at the current available evidence which exists and give much-needed guidance to both healthcare professionals and the public on these two topics.

“It is important that patients receive full information about treatments, the current evidence for benefit and whether there are any side effects or risks associated with it.”

Mr Mostafa Metwally, Vice Chair of the RCOG’s Scientific Advisory Committee added:

“There is currently no convincing evidence that uterine natural killer cells are the cause of reproductive failure. Despite this, a number of women are requesting and being offered analysis of either peripheral blood or uterine killer cells and the value of these measurements remains controversial.

“Current evidence suggests that endometrial scratch may benefit women with recurrent implantation failure and therefore defining the optimal number of previously failed embryo transfer cycles needs to be evaluated in large cohort randomised prospective clinical trials.

“We still do not understand the mechanism by which endometrial trauma may lead to improvements in IVF outcomes in women and further studies are needed looking specifically at its success among women undergoing their first IVF cycle.”


For media enquiries and copies of the papers, please contact the RCOG press office on 020 7772 6444/375 or email


The papers are available here:

The Role of Natural Killer Cells in Human Fertility (Scientific Impact Paper No. 53)

Local Endometrial Trauma (Endometrial Scratch): A Treatment Strategy to Improve Implantation Rates (Scientific Impact Paper No. 54)

RCOG Scientific Impact Papers (formerly SAC Opinion papers) are produced by the Scientific Advisory Committee. They are up-to-date reviews of emerging or controversial scientific issues of relevance to obstetrics and gynaecology, together with the implications for future practice. These documents have been rebranded to raise awareness of the issues in obstetrics and gynaecology discussed in the documents and to more accurately reflect their content and remit of the Committee.

The Royal College of Obstetricians and Gynaecologists is a medical charity that champions the provision of high quality women’s healthcare in the UK and beyond. It is dedicated to encouraging the study and advancing the science and practice of obstetrics and gynaecology. It does this through postgraduate medical education and training and the publication of clinical guidelines and reports on aspects of the specialty and service provision.